Survival outcomes of neoadjuvant immunochemotherapy versus chemotherapy for locally advanced esophageal squamous cell carcinoma.

PURPOSE: Neoadjuvant chemotherapy (NCT) is the standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Some studies reported neoadjuvant immunochemotherapy (NICT) could improve pathological response with manageable safety. However, few studies have compared the efficacy and safety of NICT and NCT, especially survival outcomes. In this study, we compared the efficacy and safety of NICT and NCT after a median follow-up of 36.0 months. METHODS: This was a retrospective study with a 1:1 propensity score matching (PSM). Locally advanced ESCC patients treated with neoadjuvant sintilimab plus chemotherapy or chemotherapy followed by esophagectomy were reviewed. The primary outcome was recurrence-free survival (RFS). RESULTS: Forty-five patients were identified in each group by PSM. The pathological complete response (pCR) rate in NICT and NCT group were 28.9% and 8.9% (P = 0.02). The hazard ratio (HR) was 0.396 (95% CI 0.171-0.919, p = 0.025) for RFS and 0.377 (95% CI 0.145-0.981, p = 0.038) for overall survival (OS), 3-year RFS was 80.6% and 62.1%, 3-year OS was 86.2% and 68.1%. Patients with pCR, MPR or downstaging had better 3-year RFS and 3-year OS. The incidences of postoperative complications and treatment-related adverse events (TRAEs) were similar. CONCLUSION: This trial preliminarily shows that NICT improves pathological and survival outcomes over NCT for resectable locally advanced ESCC, with acceptable and manageable safety.

Oblique conformal anastomosis decreased the risks of cervical anastomotic leakage after totally minimally invasive esophagectomy.

OBJECTIVE: To investigate the effectiveness of the original oblique conformal anastomosis presented in this research in reducing the incidence of cervical anastomotic leak after performing totally minimally invasive esophagectomy (TMIE). METHODS: The esophagus and stomach of 27 fresh pigs, termed the esophagogastric model, were used to simulate human esophagogastric organs for this study's in vitro experimental objectives. Nine esophagogastric models of similar weight were divided into three groups. Esophagogastrostomy with circular-stapled end-to-side anastomosis was performed. A tension gauge was used to pull the anastomosis, and the tension at which anastomotic leakage occurred was recorded. Furthermore, a retrospective assessment of 539 patients who underwent TMIE was conducted to analyze the influencing factors of cervical anastomotic leakage. RESULTS: Experiments on the esophagogastric models showed a higher fracture strength of oblique conformal anastomosis than that of conventional anastomosis (F2,18 = 40.86, P < 0.05), which was associated with a lower incidence of cervical anastomotic leakage (X2 = 9.0260, P = 0.0027). Retrospective analysis of 539 esophageal cancer patients who underwent TMIE showed that in contrast to conventional anastomosis, oblique conformal anastomosis was an independent protective factor against cervical anastomotic leakage (P = 0.0462, OR = 0.5872, 95% CI = 0.3497-0.9993). CONCLUSION: Oblique conformation anastomosis was stronger and involved a more prominent reduced risk of cervical anastomotic leakage than conventional anastomosis after TMIE.

Using molecular characteristics to distinguish multiple primary lung cancers and intrapulmonary metastases.

Objectives: Multiple lung cancers may present as multiple primary lung cancers (MPLC) or intrapulmonary metastasis (IPM) with variations in clinical stage, treatment, and prognosis. However, the existing differentiation criteria based on histology do not fully meet the clinical needs. Next-generation sequencing (NGS) may play an important role in assisting the identification of different pathologies. Here, we extended the relevant data by combining histology and NGS to develop detailed identification criteria for MPLC and IPM. Materials and Methods: Patients with lung cancer (each patient had ≥2 tumors) were enrolled in the training (n = 22) and validation (n = 13) cohorts. Genomic profiles obtained from 450-gene-targeted NGS were analyzed, and the new criteria were developed based on our findings and pre-existing Martini & Melamed criteria and molecular benchmarks. Results: The analysis of the training cohort indicated that patients identified with MPLC had no (or <2) trunk or shared mutations. However, 98.02% of mutations were branch mutations, and 69.23% of MPLC had no common mutations. In contrast, a higher percentage of trunk (33.08%) or shared (9.02%) mutations were identified in IPM, suggesting significant differences among mutated components. Subsequently, eight MPLC and five IPM cases were identified in the validation cohort, aligning with the independent imaging and pathologic distinction. Overall, the percentage of trunk and shared mutations was higher in patients with IPM than in patients with MPLC. Based on these results and the establishment of new determination criteria for MPLC and IPM, we emphasize that the type and number of shared variants based on histologic consistency assist in identification. Conclusion: Determining genetic alterations may be an effective method for differentiating MPLC and IPM, and NGS can be used as a valuable assisting tool.

SQLE is a promising prognostic and immunological biomarker and correlated with immune Infiltration in Sarcoma.

Squalene epoxidase (SQLE) is an essential enzyme involved in cholesterol biosynthesis. However, its role in sarcoma and its correlation with immune infiltration remains unclear. All original data were downloaded from The Cancer Genome Atlas (TCGA). SQLE expression was explored using the TCGA database, and correlations between SQLE and cancer immune characteristics were analyzed via the TISIDB databases. Generally, SQLE is predominantly overexpressed and has diagnostic and prognostic value in sarcoma. Upregulated SQLE was associated with poorer overall survival, poorer disease-specific survival, and tumor multifocality in sarcoma. Mechanistically, we identified a hub gene that included a total of 82 SQLE-related genes, which were tightly associated with histone modification pathways in sarcoma patients. SQLE expression was negatively correlated with infiltrating levels of dendritic cells and plasmacytoid dendritic cells and positively correlated with Th2 cells. SQLE expression was negatively correlated with the expression of chemokines (CCL19 and CX3CL1) and chemokine receptors (CCR2 and CCR7) in sarcoma. In conclusion, SQLE may be used as a prognostic biomarker for determining prognosis and immune infiltration in sarcoma.

Computed tomography radiomics identification of T1-2 and T3-4 stages of esophageal squamous cell carcinoma: two-dimensional or three-dimensional?

BACKGROUND: To evaluate two-dimensional (2D) and three-dimensional (3D) computed tomography (CT) radiomics analysis for the T stage of esophageal squamous cell carcinoma (ESCC). METHODS: 398 patients with pathologically confirmed ESCC were divided into training and testing sets. All patients underwent chest CT scans preoperatively. For each tumor, based on CT images, a 2D region of interest (ROI) was outlined on the largest cross-sectional area, and a 3D ROI was outlined layer by layer on each section of the tumor. The radiomics platform was used for feature extraction. For feature selection, stepwise logistic regression was used. The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of the 2D radiomics model versus the 3D radiomics model. The differences were compared using the DeLong test. The value of the clinical utility of the two radiomics models was evaluated. RESULTS: 1595 radiomics features were extracted. After screening, two radiomics models were constructed. In the training set, the difference between the area under the curve (AUC) of the 2D radiomics model (AUC = 0.831) and the 3D radiomics model (AUC = 0.830) was not statistically significant (p = 0.973). In the testing set, the difference between the AUC of the 2D radiomics model (AUC = 0.807) and the 3D radiomics model (AUC = 0.797) was also not statistically significant (p = 0.748). A 2D model was equally useful as a 3D model in clinical situations. CONCLUSION: The performance of 2D radiomics model is comparable to that of 3D radiomics model in distinguishing between the T1-2 and T3-4 stages of ESCC. In addition, 2D radiomics model may be a more feasible option due to the shorter time required for segmenting the ROI.

G-U base-paired hpRNA confers potent inhibition of small RNA function in plants.

MicroRNA (miRNA) target mimicry technologies, utilizing naturally occurring miRNA decoy molecules, represent a potent tool for analyzing miRNA function. In this study, we present a highly efficient small RNA (sRNA) target mimicry design based on G-U base-paired hairpin RNA (hpG:U), which allows for the simultaneous targeting of multiple sRNAs. The hpG:U constructs consistently generate high amounts of intact, polyadenylated stem-loop (SL) RNA outside the nuclei, in contrast to traditional hairpin RNA designs with canonical base pairing (hpWT), which were predominantly processed resulting in a loop. By incorporating a 460-bp G-U base-paired double-stranded stem and a 312-576 nt loop carrying multiple miRNA target mimicry sites (GUMIC), the hpG:U construct displayed effective repression of three Arabidopsis miRNAs, namely miR165/166, miR157, and miR160, both individually and in combination. Additionally, a GUMIC construct targeting a prominent cluster of siRNAs derived from cucumber mosaic virus (CMV) Y-satellite RNA (Y-Sat) effectively inhibited Y-Sat siRNA-directed silencing of the chlorophyll biosynthetic gene CHLI, thereby reducing the yellowing symptoms in infected Nicotiana plants. Therefore, the G-U base-paired hpRNA, characterized by differential processing compared to traditional hpRNA, acts as an efficient decoy for both miRNAs and siRNAs. This technology holds great potential for sRNA functional analysis and the management of sRNA-mediated diseases.

A versatile LTF-GO/gel hydrogel with antibacterial and antioxidative attributes for skin wound healing.

Skin wound healing will become a pressing and difficult problem following injury to the skin structure. Persistent wounds, in particular, become more vulnerable to bacterial infections, which can contribute to persistent skin inflammation. Therefore, it is critical to create a wound dressing that promotes wound healing while also being antimicrobial. In the present work, a multifunctional biological activity hydrogel formed by enzymatic cross-linking was developed by introducing graphene oxide (GO) and lactoferrin to gelatin hydrogel. Furthermore, by incorporating lactoferrin, the composite hydrogels exhibit excellent in vitro antibacterial and biocompatibility. According to cell experiments, the LTF-GO/Gel hydrogel can improve wound healing by enhancing L929 cell migration. Interestingly, under near-infrared light, LTF-GO/Gel hydrogel increases the generation of singlet oxygen (1O2) and hydroxyl radical (-OH), making the hydrogel system excellent antioxidant and antibacterial capabilities, these results demonstrate that the LTF-GO/Gel hydrogel has clinical promise as a wound dressing for wound healing. In vivo experiments unequivocally establish the capacity of the LTF-GO/Gel hydrogel to expedite wound healing and mitigate inflammation. This hydrogel, therefore, harbors immense potential for applications in wound healing.

Umbilical artery cord blood glucose predicted hypoglycemia in gestational diabetes mellitus and other at-risk newborns.

BACKGROUND: To explore the value of umbilical artery cord blood glucose (UACBG) in predicting hypoglycemia in gestational diabetes mellitus (GDM) and other at-risk newborns, and to provide a cut-off UACBG value for predicting hypoglycemia occurrence. METHODS: In this prospective study, we enrolled at-risk infants delivered vaginally, including neonates born to mothers with GDM, premature, macrosomic, and low birth weight. We separated the infants into GDM group and other at-risk group. All subjects underwent UACBG measurement during delivery. Neonatal peripheral blood glucose measurement was performed at 0.5 and 2 h after birth. The predictive performance of UACBG for neonatal hypoglycemia was assessed using receiver operating characteristic curve (ROC), area under curve (AUC), sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV). RESULTS: 916 newborns were included, with 538 in GDM group and 378 in other at-risk group. 85 neonates were diagnosed hypoglycemia within 2 h after birth, including 36 belonging to GDM group and 49 to other at-risk group. For hypoglycemia prediction within 2 h, the best cut-off of UACBG was 4.150 mmol/L, yielding an AUC of 0.688 (95% CI 0.625-0.751) and a NPV of 0.933. In detail, the AUC was 0.680 in GDM group (95% CI 0.589-0.771), with the optimal cut-off of 4.150 mmol/L and a NPV of 0.950. In other at-risk group, the AUC was 0.678(95% CI 0.586-0.771), the best threshold was 3.950 mmol/L and the NPV was 0.908. No significant differences were observed between GDM group and other at-risk group in AUC at 0.5 h, 2 h and within 2 h. CONCLUSIONS: UACBG has a high NPV for predicting neonatal hypoglycemia within 2 h after birth. It was implied that individuals with cord blood glucose levels above the threshold were at lower risk for hypoglycemia. UACBG monitoring provides evidence for subsequent classified management of hypoglycemia.

Trajectory of prenatal anxiety and depression and its association with fetal growth development.

BACKGROUND: The stability of anxiety and depression during pregnancy and the impact on women and offspring has been recognized, yet the distinction of impact between them remains unclear. The aim of this study was to investigate the trajectory of prenatal anxiety and depression and their coexistence, as well as to examine the potential variations in pregnancy outcomes and fetal/neonatal growth development. METHOD: At baseline (11-13+6 weeks), women were recruited and subsequently monitored in the second (16-20+6 weeks) and third (28-31+6 weeks) trimesters. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. In the second (16-20+6 weeks), third (28-31+6 weeks), and prenatal period (37-40+6 weeks), fetal growth was assessed by ultrasound scans. The joint trajectory model was used to determine the trajectory groups of depressive/anxiety dominant or coexistence. Comparisons of fetal/neonatal growth between groups were conducted using analysis of covariance and a multilevel model. RESULT: A total of 457 pregnant women were finally included. Four trajectory groups were identified: none-negative emotion (n = 190, 41.6 %), anxiety dominant (n = 195, 42.6 %), depression dominant (n = 33, 7.2 %), and anxiety and depression coexistence (n = 39, 8.6 %). There were significant differences in the antenatal abdominal circumference (335.44 vs 333.92 vs 330.82 vs 325.13 mm, p = 0.007) of fetuses and the birth length (50.14 vs 50.03 vs 49.91 vs 49.18, p = 0.008) of newborns among four groups, showing a clear decreasing trend. Anxiety and depression coexistence displayed a notable and statistically significant difference when compared to the other groups and had a lower increase of fetal abdominal circumference (ß = -8.91, 95%CI: -16.15, -1.67, p = 0.016) after controlling for confounding factors. Anxiety and depression dominant groups found no difference in fetal/neonatal growth. CONCLUSIONS: The more severe the negative emotional state of mothers, the more restricted their offspring's development, especially in terms of fetal abdominal circumference and birth length. The impact of anxiety or depressive symptoms does not show a pronounced difference. However, what is noteworthy is the tendency and evident impact on offspring development when anxiety and depression coexistence work synergistically. As a result, healthcare professionals should place greater emphasis on addressing anxiety and depression in expectant mothers, particularly among those experiencing anxiety and depression coexisting symptoms.

Deep learning based channel estimation method for mine OFDM system.

In this paper, we present a channel estimation approach based on deep learning to solve the problem that the orthogonal frequency division multiplexing (OFDM) system channel estimation algorithm cannot accurately obtain the channel state information in the complex environment of the mine, resulting in system performance degradation. First, LS channel estimation matrix is considered as a low-resolution image and the actual channel state information is considered as a high-resolution image. Then the optimization of the LS channel estimation matrix is achieved by the FSRCNN image super-resolution algorithm. We validate the effectiveness of the proposed algorithm by conducting experiments in different channel environments, different number of pilots, and mismatched signal-to-noise ratio scenarios. The simulation results show that the proposed scheme is much better than the traditional LS channel estimation method and the DFT-LS channel estimation method, and the accuracy of the proposed scheme approaches that of the MMSE channel estimation method when the number of pilots is low.

PCSK9 promotes tumor cell proliferation and migration by facilitating CCL25 secretion in esophageal squamous cell carcinoma.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) serves an important role in maintaining plasma cholesterol levels, and fatty acid metabolism is involved in the progression of various types of cancer. In the present study, the role of PCSK9 in the development of esophageal squamous cell carcinoma (ESCC) was investigated. PCSK9 expression was compared between ESCC and normal esophageal epithelial tissues using reverse transcription-quantitative PCR. In addition, the association between PCSK9 expression and clinical staging and prognosis was assessed by immunohistochemistry. The effects of PCSK9 overexpression or knockdown on cell proliferation was evaluated using Cell Counting Kit-8 and colony formation assays. The invasion and migration of cancer cells was assessed using wound healing and Transwell assays. Western blotting was performed to evaluate changes in the expression levels of epithelial-mesenchymal transition (EMT)-related proteins. ELISA was performed to detect the effects of PCSK9 on chemokine (C-C motif) ligand 25 (CCL25) secretion. The results revealed that PCSK9 was highly expressed in ESCC tissues compared with that in normal esophageal tissues, and the high expression of PCSK9 was associated with a poor prognosis. Furthermore, PCSK9 could promote the proliferation, migration and invasion of ESCC cells in vitro. Mechanistically, PCSK9 could promote EMT by secreting CCL25. In conclusion, patients with ESCC may benefit from a novel therapeutic strategy based on these findings.

Magnetic resonance imaging findings of pulmonary sclerosing pneumocytoma: a case report and literature review.

Background: Pulmonary sclerosing pneumocytoma (PSP) is a rare lung tumor that is mostly isolated and commonly reported among middle-aged East Asian women. Recently, Immunohistochemistry (IHC) analysis has suggested that PSP is of primitive epithelial origin, most likely derived from type II alveolar air cells. Patients with PSP are generally asymptomatic and usually detected for other unrelated reasons during routine imaging. Several studies have already investigated the computed tomography (CT) features of PSP and their correlation with pathology. Magnetic resonance imaging (MRI) is a radiation-free imaging technique with important diagnostic value for specific pulmonary nodules. However, very few case reports or studies focus on the MRI findings of PSP. Case report: We reported a case of an asymptomatic 56-year-old female with a solitary, well-defined soft-tissue mass in the lower lobe of the left lung. The mass showed iso-to-high signal intensity (SI) than muscle on T1-weighted image (T1WI) and T2-weighted image (T2WI) and a much higher SI on fat-suppressed T2WI, diffusion-weighted image, and apparent diffusion coefficient image. Contrast-enhanced fat-suppressed T1WI revealed noticeable inhomogeneous progressive enhancement throughout the mass. The mass revealed early enhancement without a significant peak, followed by a plateau pattern on dynamic contrast-enhanced MRI images. The patient underwent left basal segmentectomy via thoracoscopic surgery. Histopathology and IHC results of the surgical specimen confirmed that it was a PSP. We concluded that the MRI findings of PSP might adequately reflect the different components within the tumor and aid clinicians in preoperative diagnosis and assessment. To the best of our knowledge, this is the most comprehensive case report on the MRI findings of PSP. Conclusion: The MRI findings of PSP correspond to its histopathological features. Here, we present a case of PSP with the most comprehensive MRI findings, emphasizing the importance of multiple-sequence MRI in diagnosing PSP.

Spectrum Sensing Method Based on Residual Dense Network and Attention.

To address the problems of gradient vanishing and limited feature extraction capability of traditional CNN spectrum sensing methods in deep network structures and to effectively avoid network degradation issues under deep network structures, this paper proposes a collaborative spectrum sensing method based on Residual Dense Network and attention mechanisms. This method involves stacking and normalizing the time-domain information of the signal, constructing a two-dimensional matrix, and mapping it to a grayscale image. The grayscale images are divided into training and testing sets, and the training set is used to train the neural network to extract deep features. Finally, the test set is fed into the well-trained neural network for spectrum sensing. Experimental results show that, under low signal-to-noise ratios, the proposed method demonstrates superior spectral sensing performance compared to traditional collaborative spectrum sensing methods.

Synergistic antibacterial mechanism of silver-copper bimetallic nanoparticles.

The excessive use of antibiotics in clinical settings has resulted in the rapid expansion, evolution, and development of bacterial and microorganism resistance. It causes a significant challenge to the medical community. Therefore, it is important to develop new antibacterial materials that could replace traditional antibiotics. With the advancements in nanotechnology, it has become evident that metallic and metal oxide nanoparticles (MeO NPs) exhibit stronger antibacterial properties than their bulk and micron-sized counterparts. The antibacterial properties of silver nanoparticles (Ag NPs) and copper nanoparticles (Cu NPs) have been extensively studied, including the release of metal ions, oxidative stress responses, damages to cell integrity, and immunostimulatory effects. However, it is crucial to consider the potential cytotoxicity and genotoxicity of Ag NPs and Cu NPs. Numerous experimental studies have demonstrated that bimetallic nanoparticles (BNPs) composed of Ag NPs and Cu NPs exhibit strong antibacterial effects while maintaining low cytotoxicity. Bimetallic nanoparticles offer an effective means to mitigate the genotoxicity associated with individual nanoparticles while considerably enhancing their antibacterial efficacy. In this paper, we presented on various synthesis methods for Ag-Cu NPs, emphasizing their synergistic effects, processes of reactive oxygen species (ROS) generation, photocatalytic properties, antibacterial mechanisms, and the factors influencing their performance. These materials have the potential to enhance efficacy, reduce toxicity, and find broader applications in combating antibiotic resistance while promoting public health.

Application of three-dimensional computed tomography bronchography and angiography in thoracoscopic anatomical segmentectomy of the right upper lobe: A cohort study.

Objective: Three-dimensional computed tomography bronchography and angiography (3D-CTBA) can provide detailed imaging information for pulmonary segmentectomy. This study aimed to investigate the safety and effectiveness of 3D-CTBA guidance of anatomical segmentectomy of the right upper lobe (RUL). Methods: This was a retrospective analysis of anatomical segmentectomy of the RUL at the Thoracic Surgery Department of the Fourth Hospital of Hebei Medical University from December 9, 2013, to June 2, 2021. Preoperatively, all patients underwent contrast-enhanced CT of the chest (to determine the size of the pulmonary nodule) and a lung function test. 3D-CTBA has been performed since 2018; patients with vs. without 3D-CTBA were compared. Segmentectomy was performed according to nodule location. Results: Of 139 patients (46 males and 93 females, aged 21-81 years), 93 (66.9%) completed single segmentectomy, 3 (2.2%) completed single subsegmentectomy, 29 had combined subsegmentectomy, 7 had segmentectomy combined with subsegmentectomy, and 6 had combined resection of two segments. Eighty-five (61.2%) patients underwent 3D-CTBA. 3D-CTBA cases had decreased intraoperative blood loss (67.4 ± 17.6 vs. 73.1 ± 11.0, P = 0.021) and shorter operation time (143.0 ± 10.8 vs. 133.4 ± 20.9, P = 0.001). 3D-CTBA (Beta = -7.594, 95% CI: -12.877 to -2.311, P = 0.005) and surgical procedure (Beta = 9.352, 95% CI: 3.551-15.153, P = 0.002) were independently associated with intraoperative blood loss. 3D-CTBA (Beta = -13.027, 95% CI: -18.632 to 17.422, P < 0.001) and surgical procedure (Beta = 7.072, 95% CI: 0.864-13.280, P = 0.026) were also independent factors affecting the operation time. Conclusion: Preoperative use of 3D-CTBA to evaluate the pulmonary vessels and bronchial branch patterns of the RUL decreased blood loss and procedure time and so would be expected to improve the safety and effectiveness of thoracoscopic segmentectomy.

Gestational hypertensive disease and small for gestational age infants in twin pregnancy: A systematic review and meta-analysis.

AIM: The review is to explore the connection between gestational hypertension diseases (GHD) and small for gestational age (SGA) in twin pregnancies. METHODS: According to the recommendations of PRISMA, relevant studies were systematically searched through PubMed, Web of Science, Cochrane Library, Embase from inception until January 16, 2022. Subgroup analysis was performed according to chorionicity and diagnostic criteria of SGA. Odds ratios (OR) were assessed to judge the link between GHD and SGA in twin pregnant women. A random-effect model was used to estimate the pooled hazard ratio when there was significant heterogeneity (I2  > 50%); otherwise, a fixed-effect model was conducted. RESULTS: Seven articles containing 470 589 twin pregnant women were included. The increased risk of SGA was connected to the twin pregnancies complicated with GHD (OR = 1.57, 95% confidence interval [CI] = 1.10-2.24, p = 0.01). After subgroup analysis, the connection between SGA and GHD had no statistical significance (OR = 1.17, 95% CI = 0.95-1.44, p = 0.14) when the enrolled studies using the SGA diagnosis referred to singleton birth weight, but significant (OR = 2.14, 95% CI = 1.77-2.60, p<0.001) in the group using the SGA diagnosis referred to twin birth weight. Stratified by chorionicity, SGA was relevant to GHD in the dichorionic (DC) group (OR = 1.68, 95% CI = 1.17-2.42, p = 0.005), while not in the monochorionic (MC) group (OR = 1.68, 95% CI = 0.93-3.03, p = 0.09). More future articles are warranted to confirm these outcomes. CONCLUSIONS: Our review demonstrated that GHD in DC twin pregnancies was related to an enlarged risk of SGA. Two SGA diagnosis references led to different results. Twin pregnancies complicated with GHD were at significantly higher risk of SGA when twin birth weight reference was used.

hsa_circ_0000518 Facilitates Non-Small-Cell Lung Cancer Progression via Moderating miR-330-3p and Positively Regulating SLC1A5.

Background/Aim: Non-small-cell lung cancer (NSCLC) is the principal agent of cancer deaths globally. The goal of this study was to determine how circular RNA_0000518 (circ_0000518) regulates tumor progression. Materials/Methods. circ_0000518 was selected as a study target involved in NSCLC from GEO (Gene Expression Omnibus) database. circ_0000518 level was gauged by qRT-PCR. It was confirmed as circRNA by actinomycin D inhibition and RNase R assay. Subcellular localization of circ_0000518 was identified by FISH. Cell function was determined by CCK-8, Transwell, and western blot. Glutamine metabolic factors were detected by ELISA. The target regulation relationship between genes was clarified by dual-luciferase reporter assay. In vivo models were established to evaluate the impact of circ_0000518 on tumor growth. Immunohistochemical staining for Ki67, vimentin, and E-cadherin was used to detect cell proliferation and metastasis, respectively. Results: circ_0000518 expression was enhanced in NSCLC. si-circ_0000518 inhibited cell proliferation, invasion, and glutamine metabolism. circ_0000518 functioned as a molecular sponge for miR-330-3p, and inhibition of miR-330-3p in cells markedly reversed circ_0000518 interference-mediated antitumor effects. miR-330-3p interacted with 3'-UTR of SLC1A5. miR-330-3p inhibitor-mediated protumor effect was remarkably reversed in cells after the knockdown of SLC1A5. circ_0000518 knockdown reduced glutamine, glutamate, and α-KG by targeting miR-330-3p. Intertumoral injection of circ_0000518 shRNA adeno-associated virus effectively halted xenograft tumor growth. Conclusion: The current study revealed that circ_0000518 may have a prooncogenic function in the formation and progression of NSCLC, which might be achieved through moderating the miR-330-3p/SLC1A5 axis.

Nucleotide mismatches prevent intrinsic self-silencing of hpRNA transgenes to enhance RNAi stability in plants.

Hairpin RNA (hpRNA) transgenes are the most successful RNA interference (RNAi) method in plants. Here, we show that hpRNA transgenes are invariably methylated in the inverted-repeat (IR) DNA and the adjacent promoter, causing transcriptional self-silencing. Nucleotide substitutions in the sense sequence, disrupting the IR structure, prevent the intrinsic DNA methylation resulting in more uniform and persistent RNAi. Substituting all cytosine with thymine nucleotides, in a G:U hpRNA design, prevents self-silencing but still allows for the formation of hpRNA due to G:U wobble base-pairing. The G:U design induces effective RNAi in 90-96% of transgenic lines, compared to 57-65% for the traditional hpRNA design. While a traditional hpRNA transgene shows increasing self-silencing from cotyledons to true leaves, its G:U counterpart avoids this and induce RNAi throughout plant growth. Furthermore, siRNAs from G:U and traditional hpRNA show different characteristics and appear to function via different pathways to induce target DNA methylation.

Can lymphovascular invasion be predicted by contrast-enhanced CT imaging features in patients with esophageal squamous cell carcinoma? A preliminary retrospective study.

BACKGROUND: To investigate the value of contrast-enhanced CT (CECT)-derived imaging features in predicting lymphovascular invasion (LVI) status in esophageal squamous cell carcinoma (ESCC) patients. METHODS: One hundred and ninety-seven patients with postoperative pathologically confirmed esophageal squamous cell carcinoma treated in our hospital between January 2017 and January 2019 were enrolled in our study, including fifty-nine patients with LVI and one hundred and thirty-eight patients without LVI. The CECT-derived imaging features of all patients were analyzed. The CECT-derived imaging features were divided into quantitative features and qualitative features. The quantitative features consisted of the CT attenuation value of the tumor (CTVTumor), the CT attenuation value of the normal esophageal wall (CTVNormal), the CT attenuation value ratio of the tumor-to-normal esophageal wall (TNR), the CT attenuation value difference between the tumor and normal esophageal wall (ΔTN), the maximum thickness of the tumor measured by CECT (Thickness), the maximum length of the tumor measured by CECT (Length), and the gross tumor volume measured by CECT (GTV). The qualitative features consisted of an enhancement pattern, tumor margin, enlarged blood supply or drainage vessels to the tumor (EVFDT), and tumor necrosis. For the clinicopathological characteristics and CECT-derived imaging feature analysis, the chi-squared test was used for categorical variables, the Mann-Whitney U test was used for continuous variables with a nonnormal distribution, and the independent sample t-test was used for the continuous variables with a normal distribution. The trend test was used for ordinal variables. The association between LVI status and CECT-derived imaging features was analyzed by univariable logistic analysis, followed by multivariable logistic regression and receiver operating characteristic (ROC) curve analysis. RESULTS: The CTVTumor, TNR, ΔTN, Thickness, Length, and GTV in the group with LVI were higher than those in the group without LVI (P < 0.05). A higher proportion of patients with heterogeneous enhancement pattern, irregular tumor margin, EVFDT, and tumor necrosis were present in the group with LVI (P < 0.05). As revealed by the univariable logistic analysis, the CECT-derived imaging features, including CTVTumor, TNR, ΔTN and enhancement pattern, Thickness, Length, GTV, tumor margin, EVFDT, and tumor necrosis were associated with LVI status (P < 0.05). Only the TNR (OR 8.655; 95% CI 2.125-37.776), Thickness (OR 6.531; 95% CI 2.410-20.608), and tumor margin (OR 4.384; 95% CI 2.004-9.717) were independent risk factors for LVI in the multivariable logistic regression analysis. The ROC curve analysis incorporating the above three CECT-derived imaging features showed that the area under the curve obtained by the multivariable logistic regression model was 0.820 (95% CI 0.754-0.885). CONCLUSION: The CECT-derived imaging features, including TNR, Thickness, tumor margin, and their combination, can be used as predictors of LVI status for patients with ESCC.

MicroRNA-181a-5p prevents the progression of esophageal squamous cell carcinoma in vivo and in vitro via the MEK1-mediated ERK-MMP signaling pathway.

MicroRNAs (miRNAs) have been revealed to play a crucial role in oncogenesis of esophageal squamous cell carcinoma (ESCC). However, the biological role of miR-181a-5p in ESCC is currently less explored. The current study was designed to assess whether miR-181a-5p affects ESCC progression and further investigate relevant underlying mechanisms. Based on the data of GSE161533, GSE17351, GSE75241 and GSE67269 downloaded from GEO database, MAP2K1 (MEK1) was revealed to be one overlapping gene of the top 300 DGEs. Additionally, using the predicting software, miR-181a-5p was projected as the presumed target miRNA. Immunohistochemical staining and RT-qPCR research revealed that miR-181a-5p expression was decreased in human tumor tissues relative to surrounding peri-cancerous tissues. In an in vivo experiment, miR-181a-5p mimics could inhibit tumor growth and metastasis of ESCC. Gene expression profiles in combination with gene ontology (GO) and KEGG pathway analysis revealed that MAP2K1 (MEK1) gene and ERK-MMP pathway were implicated in ESCC progression. MiR-181a-5p mimics inhibited the activity of p-ERK1/2, MMP2 and MMP9 in vivo, as shown by Western blotting and immunohistochemistry labeling. There were no variations in the expression of p-P38 and p-JNK proteins. Additionally, miR-181a-5p mimics lowered p-ERK1/2, MMP2 and MMP9 levels in ECA109 cells, which were restored by MEK1-OE lentivirus. MEK1-OE Lentivirus significantly reversed the function induced by miR-181a-5p mimics in ECA109 cells. Moreover, further investigation indicated that the capability of migration, invasion and proliferation was repressed by miR-181a-5p mimics in ECA109 cells. In short, repressed ERK-MMP pathway mediated by miR-181a-5p can inhibit cell migration, invasion and proliferation by targeting MAP2K1 (MEK1) in ESCC.